Discussion 255 



explain the effects of DNP and other uncoupHng agents on the Pasteur 

 effect. 



Potter : I would emphasize that this may not play a role in the Pasteur 

 effect. We have no data indicating a quantitative role. Dr. Racker's 

 data on a 19 per cent Pasteur effect indicates that something else might 

 be looked for. I think that in tissues other than those he used, the 

 figure may be larger. 



GreviUe : This is a slight change of front. Prof. Lipmann drew atten- 

 tion in the discussion after Dr. Racker's paper to the inhibition by DNP 

 of assimilation and growth, in strictly anaerobic systems. DNP also 

 has an effect in stimulating the lactic acid production by intact frog 

 muscle, again under strictly anaerobic conditions, as was first shown by 

 Ronzoni and Ehrenfest (1936, J. hiol. Chem., 115, 749), and later con- 

 firmed in unpublished work by Dr. Dorothy Needham and myself. 

 We found that mepacrine, another uncoupling agent, has the same 

 effect. We assumed that this effect might be due to stimulation of the 

 ATPase of the mitochondria in the cells, with consequent provision of 

 ADP. But I gather that Prof. Lipmann and Prof. Lynen frown on this 

 idea of ATPase working in the intact cell. Could somebody offer some 

 other explanation of Ronzoni and Ehrenfest's effect? 



Lipmann: I don't understand why it could not act on the ATPase. 

 You still have to transport the glycolytic ATP into the mitochondria to 

 get into this ATPase milieu and get out again. It must go in and out all 

 the time. 



Krebs: If Prof. Lipmann and others do not believe in ATPase, I 

 take it that they assume that the various mechanisms which convert 

 ATP into ADP and phosphate, are complex systems. 



Rocker: I believe Prof. Lipmann wants to go one step further. He 

 suggests that the hydrolysis of ATP by ATPase is not functional inside 

 the cells and DNP does not activate it in vivo as it does in vitro. 



Lipmann: I had that in mind, but I do not know if I can stick to it! 



GreviUe: We confirmed that DNP stimulates the ATPase activity of 

 mitochondria isolated from frog muscle. 



Magasanik: What is the general effect of DNP on gro\\i:h? In 

 Aerobacter aerogenes we have been unable to inhibit the growth of the 

 organism on glucose with DNP. We put DNP in to saturation, and 

 still the organism grew. Yet, in resting cells a very definite DNP effect 

 can be shown — there is an increased oxygen uptake and no assimilation 

 of carbohydrate. 



Lehninger : Does anyone know whether DNP inhibits assimilation in a 

 strict anaerobe? 



Slater: Prof. Lipmann has drawn attention to the important point 

 that DNP has an effect on anaerobic metabolism. This interested me 

 also some time ago. I wonder whether some of these effects could be 

 explained by a DNP-stimulated hydrolysis of what we now call X ^Y. 

 In other words, you do not believe in the ATPase reaction in the 

 cell, but a part of it, the reaction of ATP with X and I to form X ~I, 

 might be involved in the utilization of ATP formed by glycolysis or 

 fermentation. 



